Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male and female virgin rats and breeder rats with naturally-occurring diabetes, hypertension and arteriosclerosis, were made severely diabetic with a single, subcutaneous injection of alloxan (10 mg/100 g b.w.), after an 18 h fast. During five months of unrelenting diabetes, some animals became obese while others became emaciated. Only the emaciated animals survived but they were blind, their adrenal glands were hemorrhagic, hypertrophied and thrombosed, thymi involuted, kidneys swollen, hearts reduced in size while testes and ovaries were atrophic. Serum CPK, SGOT and SGPT were elevated concomitant with extensive cardiovascular damage, hepatic steatosis and generalized catabolism. Circulating triglycerides and free fatty acids were markedly elevated with total cholesterol only slightly increased. BUN and serum calcium levels were also greatly elevated. Sub-normal Cmpd. B levels indicated impaired adrenal steroidogenesis. Virgin rats developed arteriosclerosis and male and female breeder rats showed exacerbation of their pre-existing aortic sclerosis as well as P.A.N. lesions in their small-sized arteries. It is believed that severe diabetes causes exacerbation of the endogenous hormonal milieu resulting from abnormal hypothalamic-pituitary-adrenal function induced by repeated breeding, which conditions the connective tissue components of the arterial wall of rats toward accelerated degenerative changes.
 ...
PMID:Polyarteritis nodosa induced in arteriosclerotic, male and female breeder rats by chronic alloxan diabetes. 1 32

In vitro hepatic synthesis of lipids starting from 1-(14)C-acetate was studied in rats made diabetic by subcutaneous alloxan administration (175 mg/kg b.w.). A second group of diabetic rats was treated with lente insulin. In the alloxan-treated rats, a decrese was observed in hepatic incorporation of 1-(14)C-acetate into phospholipids, triglycerides and esterified cholesterol; there was an increased incorporation into nonesterified fatty acids (NEFA) and free cholesterol. Insulin administration restored lipid synthesis values to normal. On histologic examination, an intranuclear glycogenesis was observed in the hepatocytes of the alloxan-treated rats, along with severe hepatic necrosis; the latter however, only in rats sacrified on the 3rd day. Hepatic steatosis with small, medium and large droplets was present in the insulin-treated rats; signs of cellular degeneration were less evident.
 ...
PMID:Effects of insulin on hepatic lipid synthesis in alloxan diabetic rats. 39 74

Liver function tests were performed in severe and mild diabetic rats and under the influence of ATP. In mild diabetics the serum cholesterol was significantly increased, while in severe diabetes the serum cholesterol was significantly lower than in mild diabetes. The decreased serum cholesterol in severe diabetes may be an indication for the development of fatty liver. The serum alkaline phosphatase and serum bilirubin were significantly increased in both the severe and mild diabetic states, while the thymol turbidity test was insignificantly changed in both states of diabetes. Serum albumin was significantly decreased in 10 days mild diabetes, while it was insignificantly changed in 48 hrs severe diabetic animals. The effect of ATP was investigated in mild diabetes. ATP resulted in a significant increase in serum albumin and a decrease in total globulins with the resultant increase in A/G ratio. The serum alkaline phosphatase exhibited a significant reduction under the influence of ATP. The elevated cholesterol of mild diabetic rats remained significantly elevated and was not reduced by ATP, though the fat content of the liver showed a significant reduction. This may be due to more rapid mobilisation of fat from the liver under the influence of ATP. ATP showed no significant effect on serum bilirubin and thymol turbidity test. the histopathological examination of the liver revealed that administration of ATP to alloxan diabetic rats had a beneficial effect. It resulted in disappearrance of the fat globules from the liver cells.
 ...
PMID:Effect of ATP on liver function tests in experimental diabetes. 65 50

In order to investigate the combined effects of diabetes and hypertension on the pathogenesis of cardiovascular disease, adult male and female SHR rats which develop hypertension spontaneously were given a single, 10 mg or 15 mg/100 g body wt. injection of alloxan s.c. to induce moderate or severe diabetes. Insulin was deliberately withheld. Animals were examined by autopsy daily for 7 days post-alloxan and after 4 and 8 weeks. Mortality was high--only 52% of the males survived as against 80% of the females. Most deaths occurred on Day 5 and were associated with adrenal haemorrhage and hyperplasia, thymus galnd involution, fatty liver and marked hypotension despite elevated aldosterone levels. During the first week, corticosterone levels increased significantly in the male; in females they showed little change. After 4 weeks, the severly diabetic animals became emaciated and moribund; corticosterone and aldosterone levels fell to very low levels despite adrenal hyperplasia. The beta cells of the moderately diabetic animals eventually lost their ability to secrete insulin and these animals too became cachetic and moribund with concomitant elevation of lipid, glucose and BUN levels, as well as myocardial infarction, fatty liver, and generalized hyalin arteriolo-, arterio-, and nephrosclerosis. It is suggested that the combined hormonal and metabolic alterations of diabetes and hypertension reinforced one another in these spontaneously hypertensive rats, leading to intense stimulation of the hypothalamic-pituitary-adrenal system, the exacerbation of those cardiovascular degenerative changes known to be associated with uncontrolled diabetes or hypertension, eventual impaired adrenocortical steroidogenesis, hypotension and death.
 ...
PMID:Alloxan diabetes in spontaneously hypertensive rats: gravimetric, metabolic and histopathological alterations. 86 Nov 67

Young, adult, female Sprague-Dawley rats were fasted for 18 h and then given a single s.c. injection of alloxan (10 mg/100 g body weight) which promptly induced a severe state of diabetes. The animals were killed at frequent time intervals during the 7-day study period in order to record the dynamic changes in their capacity for adrenal steroidogenesis and secretion as measured by fluorometric determination of their circulating corticosterone (Cmpd B) levels as well as by thin layer chromatographic identification of cortical lipid moieties used for steroidogenesis. In addition to severe polydypsia, polyuria and polyphagia, these animals manifested super-normal glucose, triglycerides, free fatty acids and cholesterol in their blood, severe hepatic steatosis, adrenal hyperplasia with lipid depletion from the mineralocorticoid producing z. glomerulosa, thymus gland involution and complete degranulation of their insulin producing islet beta cells. Despite an initial high output of Cmpd B and despite progressive cortical hyperplasia, the serum Cmpd B levels became reduced and many of the animals succumbed suddenly, due most likely to inadequate adrenocortical steroidogenesis. Adrenocortical lipids showed a progressive accumulation of free fatty acids, di- and triglycerides, suggesting that some lipid enzymatic defect could be responsible for the lack of conversion of these lipid entities essential for proper steroidogenesis.
 ...
PMID:Adrenal glandular lipids and circulating corticosterone in severely diabetic rats. 117 54

Two trials were to study alloxan diabetes in goats. The data were grouped: 1) normal fed goats (10); 2) 48-h fasted goats (5); 3) fed goats sampled 96 h after alloxan treatment (5); and 4) goats treated with alloxan following a 48-h fast and sampled 96 h after alloxan treatment with continued fasting (3). Groups 1 and 4 exhibited the following means: serum insulin 43.9, 16.4, 9.4, and 6.7 muU/ml; blood glucose 55.0, 47.3, 219.6, and 485.6 mg/100 ml; blood ketones 4.3, 2.6, 36.6, and 28.6 mg/100 ml; blood acetate 4.7, 4.0, 42.7, and 4.9 mg/100 ml; plasma-free fatty acids 1.8, 10.0, 14.4, and 40.5 mg/100 ml; and plasma triglyceride 13.3, 7.0, 47.6, and 12.2 mg/100 ml. Liver samples from five fed goats before and 12 days after alloxan treatment exhibited the following means: phospholipid 27.5 and 26.1 mg/g; triglyceride 21.2 and 98.9 mg/g; and percent lipid 7.2 and 14.4. The diabetes was accompanied by fatty liver development and probably reduction in utilization of acetate and triglyceride in the fed animals.
 ...
PMID:Blood and liver metabolites in fed and fasted diabetic goats. 124 92

The present study was performed to evaluate the correlation between fatty liver and liver function in diabetic dogs. Experimental diabetes was induced in 14 dogs by total pancreatectomy or by alloxan administration, and partial (30%) hepatectomy was performed. Diabetic dogs were compared with control dogs (N = 7) subjected only to partial hepatectomy (30%). Control and diabetic dogs were submitted to the sulfobromophthalein (BSP) liver function test. Serum BSP retention was increased in diabetic dogs but there was no correlation with the extent of fatty infiltration of the liver.
 ...
PMID:Lack of correlation between the sulfobromophthalein test and fatty liver in diabetic dogs. 262 51

The dietary administration of 5% Spirulina maxima (SM) during four weeks to diabetic mice, starting one week after a single dose of alloxan, 250 mg/Kg body weight, prevented fatty liver production in male and female animals. The main action of SM was on triacylglycerol levels in serum and liver. There was also a moderate hypoglycemia in male mice. The thiobarbituric acid reactive substances also decreased in serum and liver after SM administration. There was also a decrease in the percentage of HDL in diabetic mice that was reverted by the SM administration. The sum of LDL + VLDL percentages was also partially normalized in diabetic animals by the SM administration. An additional observation was the lower incidence of adherences between the liver and the intestine loops in the diabetic mice treated with SM compared with diabetic mice without SM. Male and female mice showed differences to diabetes susceptibility and response to SM, the female being more resistant to diabetes induction by alloxan and more responsive to the beneficial effects of SM. It is worth future work of SM on humans looking for better quality of life and longer survival of diabetic patients.
 ...
PMID:Spirulina maxima prevents fatty liver formation in CD-1 male and female mice with experimental diabetes. 1150 45

This is the first report of the effects of a nonthiazolidinedione activator of peroxisome proliferator-activated receptor (PPAR) gamma, that is, FK-614 (a benzimidazole derivative), on glucose metabolism in vivo. To investigate the effect of FK-614 on peripheral and hepatic insulin action, we performed hyperinsulinemic-hyperglycemic clamp studies combined with the triple-catheter technique and a double-tracer approach in alloxan-diabetic dogs with (n=5) or without (n=6) treatment with FK-614 (0.32 mg/kg per day orally for 10 days). Throughout the experiment, insulin was infused intraportally at 18 pmol/kg per minute and hyperglycemia (approximately 11 mmol/L) was maintained by a peripheral glucose infusion. After a 45-minute basal period (period I), a portal infusion of glucose labeled with [U-14C]-glucose, was administered for 120 minutes (period II) to measure hepatic glucose uptake. This was followed by 90-minute recovery (period III). FK-614 marginally improved peripheral insulin sensitivity, did not affect hepatic glucose uptake, and surprisingly increased tracer-determined hepatic glucose production (19.0+/-5.0 vs 10.6+/-1.7 mumol/kg per minute, P<.001). Hepatic insulin extraction was decreased by FK-614 (47.8%+/-1.6% vs 55.9%+/-3.4%, P<.01), which led to greater peripheral insulin levels and glucose utilization. FK-614 treatment also decreased the daily insulin requirements (regular insulin, 0.18+/-0.01 vs 0.32+/-0.01 U/kg per day; and NPH insulin, 0.53+/-0.02 vs 0.89+/-0.04 U/kg per day; P<.001) to maintain fasting plasma glucose at approximately 10 mmol/L for 7 days before the experiments. We conclude that FK-614 treatment, at the dose used, improves peripheral glucose utilization because of an improvement in peripheral insulin sensitivity and a decrease in insulin clearance, but impairs hepatic insulin action in alloxan-induced diabetic dogs. The reason for the effects of FK-614 on hepatic glucose and insulin metabolism is unclear but they are both consistent with reports of hepatic steatosis by PPARgamma activation when unopposed by concomitant activation of PPARalpha.
 ...
PMID:FK-614, a selective peroxisome proliferator-activated receptor gamma agonist, improves peripheral glucose utilization while decreasing hepatic insulin extraction in alloxan-induced diabetic dogs. 1612 38

Livers removed from normal rats, from alloxan diabetic rats maintained on insulin for two weeks (ADI+), and from insulin-treated diabetic rats from which insulin had been withdrawn two days before use (AD) were perfused in vitro with 120 mg (468 mumoles) palmitic acid-1-C(14). Under these conditions, output of TG (triglyceride) was depressed in livers from ADI+ rats and was negligible with livers from AD animals. The total incorporation of C(14) into perfusate TG paralleled the chemical measurments of TG output. The concentration of hepatic TG increased during perfusion of livers from normal or ADI+ rats but decreased during perfusion of livers from AD animals.A load of 120 mg of palmitic acid/3 hr was inadequate to maintain net accumulation of TG in livers from AD rats; furthermore it is implicit in this observation that the total load of NEFA (nonesterified fatty acid) perfusing livers from AD rats must be increased considerably to obtain a fatty liver. The total incorporation of C(14) into hepatic TG and the specific activity of hepatic TG were depressed during perfusion of livers from AD rats. The production of ketone bodies by livers from AD animals was about five times the normal rates; the output of ketone bodies did not differ from results of other experiments (1) in which the load of palmitic acid added to the medium was varied from 0-80 mg. These observations were discussed with reference to mechanisms for ketogenesis and fatty liver in alloxan diabetes.
 ...
PMID:Hepatic lipid metabolism in experimental diabetes: III. Synthesis and utilization of triglycerides. 1780 72


1